Ciliary Neurotrophic Factor Mediates Dopamine D2Receptor-Induced CNS Neurogenesis in Adult Mice

• DOI: 10.1523/jneurosci.3574-07.2008
• Publication Date: 2008-02-27T22:25:02Z
• Authors: Peng Yang; Sheila A. Arnold; Agata Habas; Michal Hetman; Theo Hagg
• Keywords: Ciliary neurotrophic factor; Quinpirole

Neurogenesis continues in the adult forebrain subventricular zone (SVZ) and dentate gyrus of hippocampal formation. Degeneration dopaminergic projections Parkinson's disease animals reduces, whereas ciliary neurotrophic factor (CNTF) promotes, neurogenesis. We tested whether system promotes neurogenesis through CNTF. Astrocytes SVZ expressed CNTF were close to terminals. Dopaminergic denervation mice reduced mRNA by ∼60%, systemic treatment with D 2 agonist quinpirole increased formation, cultured astrocytes 1.5–5 fold. The effect vitro was blocked antagonist eticlopride did not cause astroglial proliferation or hypertrophy. Systemic injections wild-type ∼25–75% but −/− littermates infused antibodies. Quinpirole number neuroblasts littermates. ∼20% mice, confirming endogenous role Nigrostriatal affect suggesting that innervation normally regulates acted on postsynaptic receptors as it reversed seen after mice. Thus, mediates innervation- receptor-induced forebrain. Because is predominantly nervous system, this mechanism ability pharmacologically modulate have implications for cell-replacement therapies other disorders.